ifinatamab deruxtecan (DS-7300)

P1/2, N=242, Recruiting, Merck Sharp & Dohme LLC | N=138 --> 242

P2, N=144, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1/2, N=360, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

B7-H3 showed consistent, high expression across SCLC molecular subtypes, whereas DLL3 and SEZ6 expression varied significantly. These data suggest B7-H3-targeting ADCs may be active across SCLC subtypes, consistent with the high reported response rates.

P2, N=96, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1/2, N=138, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 --> Aug 2029 | Trial primary completion date: Oct 2028 --> Aug 2029

P3, N=1440, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P2, N=187, Active, not recruiting, Daiichi Sankyo | Trial completion date: Apr 2025 --> Nov 2025

P1/2, N=450, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2039 --> Feb 2032 | Trial primary completion date: Feb 2039 --> Feb 2032

Tarlatamab is a DLL3-directed bi-specific T-cell engager (BiTE) whose efficacy was evaluated in a Phase 2 study...Ifinatamab-deruxtecan is an anti-B7-H3 ADC showing efficacy in pretreated SCLC patients in a phase 2 clinical trial. Sacituzumab govitecan is a Trop-2-directed ADC already used in other tumor types and evaluated in SCLC in the phase 2 TROPiCS-03 trial, with positive results...Novel antibody-based agents could potentially acquire a prominent role in the treatment of SCLC, a field with few therapeutic options. Direct comparisons with the current standard of care still lack, however Phase 3 trials are currently ongoing.

P3, N=510, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P1/2, N=209, Not yet recruiting, Merck Sharp & Dohme LLC | Initiation date: Apr 2025 --> Aug 2025

P3, N=1440, Not yet recruiting, Merck Sharp & Dohme LLC

P1/2, N=232, Recruiting, Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: Jun 2027 --> Nov 2027 | Trial primary completion date: Jun 2027 --> Nov 2027

While investigated therapies such as rovalpituzumab tesirine (Rova-T) have failed, several insights from these trials have led to the development of compelling new agents such as sacituzumab govitecan (SG), ifinatamab deruxtecan (I-DXd), tarlatamab, and DLL3-targeted CAR-T cells. Advancing development of molecular testing and improving targeted approaches remain integral to pushing forward the progress of adoptive cell therapies in SCLC.

P1/2, N=360, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=96, Not yet recruiting, Merck Sharp & Dohme LLC | Initiation date: Feb 2025 --> May 2025

P2, N=144, Not yet recruiting, Merck Sharp & Dohme LLC | Initiation date: Feb 2025 --> May 2025 | Trial primary completion date: Sep 2030 --> Mar 2032

P1/2, N=138, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1/2, N=232, Recruiting, Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: Feb 2026 --> Jun 2027 | Trial primary completion date: Feb 2026 --> Jun 2027

P2, N=96, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=144, Not yet recruiting, Merck Sharp & Dohme LLC

P1/2, N=209, Not yet recruiting, Merck Sharp & Dohme LLC

P1/2, N=138, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=510, Not yet recruiting, Daiichi Sankyo | Trial primary completion date: May 2029 --> Jun 2028

P1/2, N=250, Recruiting, Daiichi Sankyo | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=450, Recruiting, Merck Sharp & Dohme LLC | Active, not recruiting --> Recruiting

P3, N=510, Not yet recruiting, Daiichi Sankyo

P1/2, N=450, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P2 --> P1/2

P1/2, N=149, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P2, N=520, Recruiting, Daiichi Sankyo | N=260 --> 520 | Trial primary completion date: Dec 2026 --> Jul 2028

P1/2, N=232, Recruiting, Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | N=162 --> 232 | Trial primary completion date: Jul 2025 --> Jan 2026

Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges.

P3, N=468, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P2, N=187, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

Nivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect...Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing. The standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.

P3, N=468, Not yet recruiting, Daiichi Sankyo | Trial completion date: Jan 2028 --> Feb 2029 | Trial primary completion date: Jul 2026 --> Apr 2027

P2, N=260, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P1/2, N=149, Not yet recruiting, Daiichi Sankyo

P2, N=260, Not yet recruiting, Daiichi Sankyo

P2, N=180, Recruiting, Daiichi Sankyo | N=91 --> 180 | Trial completion date: Nov 2024 --> Jul 2025 | Trial primary completion date: May 2024 --> Jan 2025

P2, N=91, Recruiting, Daiichi Sankyo, Inc. | Active, not recruiting --> Recruiting